The origin of the occupational air standard for beryllium was based on the toxicity of other heavy metals such as arsenic, lead and mercury and modified to reflect beryllium's lower atomic weight and concern about its greater toxicity. No epidemiological studies of health outcomes and exposure were used to reach a consensus on the initial recommended air standard of 2ug/m"3. Almost 50 years later this remains the current air level that OHSA and DOE enforce in the work place. Most recent studies looking at beryllium disease and exposure have used surrogates of exposure and found increased disease with increased exposure. In addition, the contributions of host factors have been examined in an unvariate fashion without simultaneously examining exposure levels. Chronic beryllium disease can now be diagnosed using proliferation lymphocyte tests from either the lung lavage fluid or peripheral blood. However, follow-up studies to characterize the clinical significance of positive findings of the proliferation tests are needed. This project will investigate possible exposure-response relationships for various measures of exposure, including chemical and physical form, beryllium sensitization and clinical disease. Host factors will be examined in conjunction with exposure data to better address the issue of host susceptibility. Finally, the natural history of beryllium disease in individuals with positive proliferation tests will be determined.